Most mycoplasma species with polarized cell morphologies exhibit gliding motility, a process inextricably intertwined with adherence to host cells (cytadherence) but of uncertain molecular mechanism. Moreover, different phylogenetic groups of mycoplasmas appear to adhere and glide by different mechanisms. Mycoplasma penetrans, an organism found principally in HIV-positive patients in whom it appears to potentiate the progress of AIDS by promoting proliferation of the type of cell that HIV infects, also exhibits polar morphology and is known to burrow into host epithelial cells. However, the molecular basis for its interaction with host cells is entirely unknown, its genome sequence indicating an absence of homologs of cytadherence proteins of other organisms. We have established that three different M. penetrans strains exhibit gliding motility and adherence with positive correlation between speed and strength of adherence. We have identified a detergent-insoluble structure in the leading, adherence-associated cell pole and two of its probable protein components. We will continue to identify components of this cell polarity-associated structure by mass spectrometry of detergent-insoluble proteins as well as by testing whether similar proteins encoded by adjacent genes are components. We will examine the expression of polarity-associated genes to determine whether they are cotranscribed, and we will identify further virulence-associated genes of M. penetrans through microarray data, comparing bacteria grown axenically with bacteria grown in the presence of host cells. Finally, we will obtain genome sequences for the two M. penetrans strains that are not yet sequenced, and use comparative analysis to identify candidate genes for adhesins and motor proteins. The results of these experiments will shed light on generation of cellular polarity, cellular motility, and the means by which M. penetrans might contribute to the sickness of AIDS patients in hopes of rational design of inhibitors of this likely cofactor. PUBLIC HEALTH RELEVANCE: Although for some bacteria it is understood how they move and how they attach to the cells of people they infect, mycoplasmas behave differently from other bacteria, and different types of mycoplasmas behave differently from one another. Mycoplasma penetrans is usually found in patients infected with HIV, which causes AIDS, and is believed to cause those patients'disease to progress faster than individuals without M. penetrans infection. In this study, we will identify molecules associated with adherence of M. penetrans to the cells of its host, movement of M. penetrans, and the ability of M. penetrans to cause disease in general.